Review

. 2016 Jan 28:7:19.

doi: 10.1186/s13287-015-0273-0.

Combining regenerative medicine strategies to provide durable reconstructive options: auricular cartilage tissue engineering

Zita M Jessop^{1

2}, Muhammad Javed^{3

4}, Iris A Otto^{5

6}, Emman J Combellack^{7

8}, Siân Morgan^{9

10}, Corstiaan C Breugem¹¹, Charles W Archer¹², Ilyas M Khan¹³, William C Lineaweaver¹⁴, Moshe Kon¹⁵, Jos Malda^{16

17}, Iain S Whitaker^{18

19}

Affiliations

¹ Reconstructive Surgery & Regenerative Medicine Research Group, Swansea University Medical School, Room 509, ILS2, Swansea, SA2 8SS, UK. zitajessop@gmail.com.
² The Welsh Centre for Burns and Plastic Surgery, Morriston Hospital, Swansea, SA6 6NL, UK. zitajessop@gmail.com.
³ Reconstructive Surgery & Regenerative Medicine Research Group, Swansea University Medical School, Room 509, ILS2, Swansea, SA2 8SS, UK. umaidr@googlemail.co.uk.
⁴ The Welsh Centre for Burns and Plastic Surgery, Morriston Hospital, Swansea, SA6 6NL, UK. umaidr@googlemail.co.uk.
⁵ Department of Orthopaedics, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands. Otto@students.uu.nl.
⁶ Department of Plastic and Reconstructive Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. Otto@students.uu.nl.
⁷ Reconstructive Surgery & Regenerative Medicine Research Group, Swansea University Medical School, Room 509, ILS2, Swansea, SA2 8SS, UK. combellack@gmail.com.
⁸ The Welsh Centre for Burns and Plastic Surgery, Morriston Hospital, Swansea, SA6 6NL, UK. combellack@gmail.com.
⁹ Reconstructive Surgery & Regenerative Medicine Research Group, Swansea University Medical School, Room 509, ILS2, Swansea, SA2 8SS, UK. morga1985@hotmail.co.uk.
¹⁰ The Welsh Centre for Burns and Plastic Surgery, Morriston Hospital, Swansea, SA6 6NL, UK. morga1985@hotmail.co.uk.
¹¹ Department of Plastic and Reconstructive Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. Breugem@umcutrecht.nl.
¹² Reconstructive Surgery & Regenerative Medicine Research Group, Swansea University Medical School, Room 509, ILS2, Swansea, SA2 8SS, UK. archer@swansea.ac.uk.
¹³ KhanLab, Swansea University, ILS2, Swansea, SA2 8SS, UK. khan@swansea.ac.uk.
¹⁴ Division of Plastic Surgery, University of Mississippi Medical Center, Jackson, Mississippi, 39216, USA. lineaweaver@jmsburncenters.com.
¹⁵ Department of Plastic and Reconstructive Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. Kon@umcutrecht.nl.
¹⁶ Department of Orthopaedics, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands. Malda@umcutrecht.nl.
¹⁷ Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Domplein 29, 3512 JE, Utrecht, The Netherlands. Malda@umcutrecht.nl.
¹⁸ Reconstructive Surgery & Regenerative Medicine Research Group, Swansea University Medical School, Room 509, ILS2, Swansea, SA2 8SS, UK. iainwhitaker@fastmail.fm.
¹⁹ The Welsh Centre for Burns and Plastic Surgery, Morriston Hospital, Swansea, SA6 6NL, UK. iainwhitaker@fastmail.fm.

PMID: 26822227
PMCID: PMC4730656
DOI: 10.1186/s13287-015-0273-0

Review

Combining regenerative medicine strategies to provide durable reconstructive options: auricular cartilage tissue engineering

Zita M Jessop et al. Stem Cell Res Ther. 2016.

. 2016 Jan 28:7:19.

doi: 10.1186/s13287-015-0273-0.

Authors

Affiliations

¹ Reconstructive Surgery & Regenerative Medicine Research Group, Swansea University Medical School, Room 509, ILS2, Swansea, SA2 8SS, UK. zitajessop@gmail.com.
² The Welsh Centre for Burns and Plastic Surgery, Morriston Hospital, Swansea, SA6 6NL, UK. zitajessop@gmail.com.
³ Reconstructive Surgery & Regenerative Medicine Research Group, Swansea University Medical School, Room 509, ILS2, Swansea, SA2 8SS, UK. umaidr@googlemail.co.uk.
⁴ The Welsh Centre for Burns and Plastic Surgery, Morriston Hospital, Swansea, SA6 6NL, UK. umaidr@googlemail.co.uk.
⁵ Department of Orthopaedics, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands. Otto@students.uu.nl.
⁶ Department of Plastic and Reconstructive Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. Otto@students.uu.nl.
⁷ Reconstructive Surgery & Regenerative Medicine Research Group, Swansea University Medical School, Room 509, ILS2, Swansea, SA2 8SS, UK. combellack@gmail.com.
⁸ The Welsh Centre for Burns and Plastic Surgery, Morriston Hospital, Swansea, SA6 6NL, UK. combellack@gmail.com.
⁹ Reconstructive Surgery & Regenerative Medicine Research Group, Swansea University Medical School, Room 509, ILS2, Swansea, SA2 8SS, UK. morga1985@hotmail.co.uk.
¹⁰ The Welsh Centre for Burns and Plastic Surgery, Morriston Hospital, Swansea, SA6 6NL, UK. morga1985@hotmail.co.uk.
¹¹ Department of Plastic and Reconstructive Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. Breugem@umcutrecht.nl.
¹² Reconstructive Surgery & Regenerative Medicine Research Group, Swansea University Medical School, Room 509, ILS2, Swansea, SA2 8SS, UK. archer@swansea.ac.uk.
¹³ KhanLab, Swansea University, ILS2, Swansea, SA2 8SS, UK. khan@swansea.ac.uk.
¹⁴ Division of Plastic Surgery, University of Mississippi Medical Center, Jackson, Mississippi, 39216, USA. lineaweaver@jmsburncenters.com.
¹⁵ Department of Plastic and Reconstructive Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. Kon@umcutrecht.nl.
¹⁶ Department of Orthopaedics, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands. Malda@umcutrecht.nl.
¹⁷ Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Domplein 29, 3512 JE, Utrecht, The Netherlands. Malda@umcutrecht.nl.
¹⁸ Reconstructive Surgery & Regenerative Medicine Research Group, Swansea University Medical School, Room 509, ILS2, Swansea, SA2 8SS, UK. iainwhitaker@fastmail.fm.
¹⁹ The Welsh Centre for Burns and Plastic Surgery, Morriston Hospital, Swansea, SA6 6NL, UK. iainwhitaker@fastmail.fm.

PMID: 26822227
PMCID: PMC4730656
DOI: 10.1186/s13287-015-0273-0

Abstract

Recent advances in regenerative medicine place us in a unique position to improve the quality of engineered tissue. We use auricular cartilage as an exemplar to illustrate how the use of tissue-specific adult stem cells, assembly through additive manufacturing and improved understanding of postnatal tissue maturation will allow us to more accurately replicate native tissue anisotropy. This review highlights the limitations of autologous auricular reconstruction, including donor site morbidity, technical considerations and long-term complications. Current tissue-engineered auricular constructs implanted into immune-competent animal models have been observed to undergo inflammation, fibrosis, foreign body reaction, calcification and degradation. Combining biomimetic regenerative medicine strategies will allow us to improve tissue-engineered auricular cartilage with respect to biochemical composition and functionality, as well as microstructural organization and overall shape. Creating functional and durable tissue has the potential to shift the paradigm in reconstructive surgery by obviating the need for donor sites.

PubMed Disclaimer

Figures

**Fig. 1**
Limitations of current tissue-engineered auricular cartilage constructs

**Fig. 2**
Histology of bovine auricular cartilage (haematoxylin and eosin staining). a Immature bovine auricular cartilage demonstrating homogeneous cell organization and high cell density. b Mature bovine auricular cartilage showing depth-dependent cell density and organization

**Fig. 3**
Three-dimensional-printed complex anatomical structures based on polycaprolactone (PCL) with polyvinyl alcohol (PVA) support. a–c Vascular tree. d–f Right ear. g–i DNA helix. a, d, g Computer-aided designs showing permanent (*red*) and sacrificial (*grey*) components. b, e, h Printed structures showing PCL (*bright white*) and PVA (*off-white*). d, f, i PCL scaffold after sacrificing PVA support. Reproduced with permission from Visser et al. [131] and Institute of Physics Publishing

See this image and copyright information in PMC

Cited by

The application and progress of stem cells in auricular cartilage regeneration: a systematic review.
Liu Y, Wu W, Seunggi C, Li Z, Huang Y, Zhou K, Wang B, Chen Z, Zhang Z. Liu Y, et al. Front Cell Dev Biol. 2023 Jul 26;11:1204050. doi: 10.3389/fcell.2023.1204050. eCollection 2023. Front Cell Dev Biol. 2023. PMID: 37564374 Free PMC article. Review.
Alginate Conjugation Increases Toughness in Auricular Chondrocyte Seeded Collagen Hydrogels.
Slyker L, Bonassar LJ. Slyker L, et al. Bioengineering (Basel). 2023 Sep 4;10(9):1037. doi: 10.3390/bioengineering10091037. Bioengineering (Basel). 2023. PMID: 37760139 Free PMC article.
Full-Field Strain Uncertainties and Residuals at the Cartilage-Bone Interface in Unstained Tissues Using Propagation-Based Phase-Contrast XCT and Digital Volume Correlation.
Tozzi G, Peña Fernández M, Davis S, Karali A, Kao AP, Blunn G. Tozzi G, et al. Materials (Basel). 2020 Jun 5;13(11):2579. doi: 10.3390/ma13112579. Materials (Basel). 2020. PMID: 32516970 Free PMC article.
Biofabrication of a shape-stable auricular structure for the reconstruction of ear deformities.
Otto IA, Capendale PE, Garcia JP, de Ruijter M, van Doremalen RFM, Castilho M, Lawson T, Grinstaff MW, Breugem CC, Kon M, Levato R, Malda J. Otto IA, et al. Mater Today Bio. 2021 Jan 21;9:100094. doi: 10.1016/j.mtbio.2021.100094. eCollection 2021 Jan. Mater Today Bio. 2021. PMID: 33665603 Free PMC article.
Endocrine Petrified Ear: Associated Endocrine Conditions in Auricular Calcification/Ossification (A Sample-Focused Analysis).
Valea A, Nistor C, Ciobica ML, Sima OC, Carsote M. Valea A, et al. Diagnostics (Basel). 2024 Jun 19;14(12):1303. doi: 10.3390/diagnostics14121303. Diagnostics (Basel). 2024. PMID: 38928718 Free PMC article. Review.

See all "Cited by" articles

References

1. Moroni L, Hamann D, Paoluzzi L, Pieper J, de Wijn JR, van Blitterswijk CA. Regenerating articular tissue by converging technologies. PLoS One. 2008;3(8):e3032. doi: 10.1371/journal.pone.0003032. - DOI - PMC - PubMed
1. Biophoenix . Opportunities in stem cell research and commercialisation. London: Business Insights; 2006. p. 80.
1. Togo T, Utani A, Naitoh M, Ohta M, Tsuji Y, Morikawa N, et al. Identification of cartilage progenitor cells in the adult ear perichondrium: utilization for cartilage reconstruction. Lab Invest. 2006;86(5):445–57. doi: 10.1038/labinvest.3700409. - DOI - PubMed
1. Ruszymah BHI, Lokman BS, Asma A, Munirah S, Chua K, Mazlyzam AL, et al. Pediatric auricular chondrocytes gene expression analysis in monolayer culture and engineered elastic cartilage. Int J Pediatr Otorhinol. 2007;71(8):1225–34. doi: 10.1016/j.ijporl.2007.04.014. - DOI - PubMed
1. Bichara DA, O’Sullivan NA, Pomerantseva I, Zhao X, Sundback CA, Vacanti JP, et al. The tissue-engineered auricle: past, present, and future. Tissue Eng Part B Rev. 2012;18:51–61. doi: 10.1089/ten.teb.2011.0326. - DOI - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Combining regenerative medicine strategies to provide durable reconstructive options: auricular cartilage tissue engineering

Affiliations

Combining regenerative medicine strategies to provide durable reconstructive options: auricular cartilage tissue engineering

Authors

Affiliations

Abstract

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources